(R)-N-(4-nitrophenoxycarbonyl)glutamic acid di-tert-butyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-N-(4-nitrophenoxycarbonyl)glutamic acid di-tert-butyl ester
• 英文别名: ditert-butyl (2R)-2-[(4-nitrophenoxy)carbonylamino]pentanedioate
• 化学式: C₂₀H₂₈N₂O₈
• 分子量: 424.451
• InChiKey: WHAZJZXGZDOOFV-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R)-N-(4-nitrophenoxycarbonyl)glutamic acid di-tert-butyl ester 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.17h， 生成 (R)-2-(4-Methoxy-phenylsulfanylcarbonylamino)-pentanedioic acid
  参考文献：
  名称：

  Novel Inhibitors of Carboxypeptidase G₂ (CPG₂):  Potential Use in Antibody-Directed Enzyme Prodrug Therapy

  摘要：

  The design and synthesis of potent thiocarbamate inhibitors for carboxypeptidase Ga are described. The best thiocarbamate inhibitor N-(p-methoxybenzenethiocarbonyl)amino-L-glutamic acid 6d, chosen for preliminary investigations of in vitro antibody-directed enzyme prodrug therapy (ADEPT), abrogated the cytotoxicity of a combination of A5B7-carboxypeptidase G(2) conjugate and prodrug PGP (N-p-{N,N-bis (2-chloroethyl)amino}phenoxycarbonyl-L-glutamate) toward LS174T cells. This is the first report of a small-molecule enzyme inhibitor proposed for use in conjunction with the ADEPT approach.

  DOI：

  10.1021/jm990004i
• 作为产物：
  描述：

  二(对硝基苯)碳酸酯 、 (R)-2-氨基戊二酸二叔丁酯 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 (R)-N-(4-nitrophenoxycarbonyl)glutamic acid di-tert-butyl ester
  参考文献：
  名称：

  Water-Soluble and Cleavable Quercetin–Amino Acid Conjugates as Safe Modulators for P-Glycoprotein-Based Multidrug Resistance

  摘要：

  Quercetinamino acid conjugates with alanine or glutamic acid moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects were evaluated. A quercetinglutamic acid conjugate, 7-O-Glu-Q (3a), was as potent as verapamil in reversing MDR and sensitized MDR MES-SA/Dx5 cells to various anticancer drugs with EC50 values of 0.80.9 mu M. Analysis on Rh-123 accumulation confirmed that 3a inhibits drug efflux by Pgp, and Pgp ATPase assay showed that 3a interacts with the drug-binding site of Pgp to stimulate its ATPase activity. Physicochemical analysis of 3a revealed that solubility, stability, and cellular uptake of quercetin were significantly improved by the glutamic acid promoiety, which eventually dissociates from 3a to produce quercetin and quercetin metabolites in intracellular milieu. Taken together, potent MDR-modulating activity along with intracellular conversion into the natural flavonoid quercetin warrants development of the quercetinamino acid conjugates as safe MDR modulators.

  DOI：

  10.1021/jm500290c